Iridium-catalyzed highly enantioselective ring opening reaction of oxabenzonorbornadienes with amines

Article abstract of DOI:10.1016/j.tetasy.2015.10.017

The complex of [Ir(COD)Cl]₂ and (R)-xylyl-phanephos was used as an effective catalyst for the asymmetric ring opening reaction of oxabenzonorbornadienes with various amines. Under the optimized reaction conditions, high enantioselectivities with moderate to good yields could be obtained from a wild scope of oxabenzonorbornadienes and amines.

Full text of DOI:10.1016/j.tetasy.2015.10.017

Tetrahedron: Asymmetry 26 (2015) 1354–1359
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Iridium-catalyzed highly enantioselective ring opening reaction
of oxabenzonorbornadienes with amines
⇑
Yongyun Zhou, Zhiwu Lu, Baiqiu Han, Chaoyuan Zeng, Zhenhua Zhang, Baomin Fan
YMU-HKBU Joint Laboratory of Traditional Natural Medicine, Yunnan Minzu University, Kunming 650500, China
a r t i c l e i n f o
a b s t r a c t
Article history:
The complex of [Ir(COD)Cl]2 and (R)-xylyl-phanephos was used as an effective catalyst for the
asymmetric ring opening reaction of oxabenzonorbornadienes with various amines. Under the optimized
reaction conditions, high enantioselectivities with moderate to good yields could be obtained from a wild
scope of oxabenzonorbornadienes and amines.
Received 7 August 2015
Revised 14 October 2015
Accepted 15 October 2015
Available online 5 November 2015
Ó 2015 Elsevier Ltd. All rights reserved.
1. Introduction
iridium catalysts, especially those with high enantioselective-
control ability and a wider reaction scope, is still interesting and
As an efficient method for the construction of chiral dihydron-
aphthalenes, which are important building blocks in the synthesis
of natural products or bioactive molecules, the transitional metal
catalyzed asymmetric ring opening reactions of oxa/azabenzonor-
bornadienes with various nucleophiles have been extensively stud-
ied. Notable successes have been achieved for the asymmetric ring
opening reactions with carbo-nucleophiles in the past few decades.
For instance, many efficient chiral catalysts had been developed
based on Pd,1 Rh,2 Cu,3 Pt4 and Ni5 for the same or different
carbo-nucleophiles. However, only rhodium catalysts bearing chi-
ral ferrocenyl diphosphine ligands, which were developed by Laut-
ens et al. were found efficient for asymmetric ring opening
reactions with hetero-nucleophiles over a relatively long period
of time.6 Changes have appeared in the last few years. In addition
to new rhodium catalysts with chiral monophosphine ligands,
which were established by Luo et al.7 some chiral iridium com-
plexes have been employed as catalysts in this type of reactions.
For example, the iridium catalysts possessing Binap family ligands
were reported by Yang et al. to promote the asymmetric ring open-
ing reactions of oxa/azabenzonorbornadienes with several hetero-
nucleophiles smoothly.8 The complexes of [Ir(COD)Cl]2 with some
monophosphine ligands were also found to be suitable catalysts for
these reactions by Tang et al.9 and by our own group.10 Recently,
by using Lewis acid as co-catalyst, a new iridium catalytic system
was also established for the asymmetric ring opening reaction of
azabenzonorbornadienes with amines.11 However, these iridium
catalysts encountered unstable catalytic activity to the reaction
enantioselectivities or yields, and one of them lacked the tolerance
of a wide scope of amines. Thus, further development of new chiral
necessary.
Recently, our group has been attracted by the transitional metal
catalyzed asymmetric reactions of norbornadiene derivatives. We
have developed several efficient chiral catalysts or catalytic sys-
tems for asymmetric [2+2] cycloaddition reactions,12 hydroalkyny-
lation reactions13 and alkynylative ring opening reactions14 of
norbornadiene derivatives with terminal alkynes. During the
course of our investigation on the [Ir(COD)Cl]2/(R)-xylyl-phanephos
complex catalyzed asymmetric [2+2] cycloaddition reactions of
oxabenzonorbornadienes, we found that this complex could also
promote some asymmetric ring opening reactions with hetero-
nucleophiles. Herein, we report the results of the application of this
iridium catalyst in the asymmetric ring opening reaction of
oxabenzonorbornadienes with amines.
2. Results and discussion
Initially, under the former optimized reaction conditions for the
[2+2] cycloaddition reaction,12 the complex of [Ir(COD)Cl]2 and
(R)-xylyl-phanephos15 was tested in the asymmetric ring opening
reaction of oxabenzonorbornadiene 1a with N-methylaniline 2a.
After stirring at 70 °C for 22 hours, the aimed ring opening product
3aa was obtained in 68% yield and with 92% ee (Table 1, entry 1).
With this encouraging result in hand, the reaction conditions
were further optimized. Besides THF (tetrahydrofuran), DMAc
(N,N-dimethylacetamide), DMF (N,N-dimethylformamide), DME
(dimethoxyethane), THP (tetrahydropyran) and toluene all
provided the expected product in moderate yields with good ees
(Table 1, entries 2–6). DCE (1,2-dichloroethane) was proved
inferior here (Table 1, entry 7). In all the solvents screened, dioxane
gave the highest enantioselectivity with a good yield (Table 1,
entry 8). The temperature effect was then studied using dioxane
⇑
Corresponding author. Fax: +86 8716594.
E-mail address: adams.bmf@hotmail.com (B.M. Fan).
http://dx.doi.org/10.1016/j.tetasy.2015.10.017
0957-4166/Ó 2015 Elsevier Ltd. All rights reserved.

Y. Zhou et al. / Tetrahedron: Asymmetry 26 (2015) 1354–1359
1355
Table 1
Table 2
Screening reaction conditionsa
Asymmetric ring opening reactions of 1a with different aminesa,b
R3
[Ir(COD)Cl]2
(R)-xylyl-phanephos
2.5 mol% [Ir(COD)Cl]2
6.5 mol% (R)-xylyl-phanephos
OH Me
N
OH
H
H
N
N
N
R4
O
Ph
O
R3
R4
dioxane, 70oC
solvent
Me
Ph
1a
2a-l
3aa
3aa-3am
1a
2a
PAr2
Entry
Amine 2
NHMe
Time (h)
Yieldc (%)
75
eed (%)
96
PAr2
1
2
22
2a
NHEt
Ar = Ph
(R)-Phanephos
Ar = 3,5-diMePh (R)-xylyl-Phanephos
23
56
30
97
96
2b
Me
Entry
Solvent
Temp (°C)
Time (h)
Yieldb (%)
eec (%)
H
N
3
24
1
2
3
4
5
6
7
8
THF
70
70
70
70
70
70
70
70
90
50
70
70
22
3
9
68
71
72
67
55
49
Trace
62
58
38
40
92
90
92
88
91
85
/
96
95
95
87
96
2c
Me
DMAc
DMF
DME
THP
Toluene
DCE
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
4
5
Br
NHMe
21
75
50
49
95
97
2d
21
21
17
78
21
5.5
125
51
22
MeO
NHMe 2e
NHMe
9
6
7
23
46
56
36
97
88
2f
10d
11e
12f
N
H
75
2g
a
The reaction was carried out with oxabenzonorbornadiene 1a (0.3 mmol) and
8
N
NH
2h
45
42
51
73
30
52
62
47
84
92
90
89
3.0 equiv of N-methylaniline (0.9 mmol) in solvent (2.0 mL) at 70 °C (oil bath
temperature) in the presence of [Ir(COD)Cl]2 (1.5 mol %) and (R)-xylyl-phanephos
(3.9 mol %).
9
NH2
2i
b
Isolated yield after neutral alumina column chromatography.
Determined by HPLC with a Chiralcel OD-H column.
The reaction was not completed.
(R)-Phanephos was used as the chiral ligand.
c
d
10
11
Me
NH2 2j
e
f
2.5 mol % [Ir(COD)Cl]2 and 6.5 mol % (R)-xylyl-phanephos was added.
MeO
Br
NH2
2k
as the solvent. Increasing the reaction temperature from 70 °C to
90 °C led to a slightly lower yield and a similar ee for the reaction
(Table 1, entry 9). Lowering the reaction temperature to 50 °C did
not improve the ee, but resulted in a great decrease in the reaction
speed. Even after 5 days of heating and stirring, a lot of 1a still
remained in the reaction solution and 3aa could only be separated
out in 38% yield (Table 1, entry 10). When (R)-phanephos was used
instead of (R)-xylyl-phanephos as the chiral ligand in the reaction,
both the yield and the enantioselectivity of the reaction decreased
(Table 1, entry 11). It was also found that increasing the catalyst
loading improved the reaction results, and a 75% yield with 96%
ee could be obtained when 5% catalyst was used (Table 1, entry 12).
With the optimal reaction conditions in hand, a series of amines
were tested as nucleophiles in the ring opening reaction of 1a
(Table 2). It could be seen that the steric properties of the alkyl
groups on the nitrogen atom in the N-alkyl substituted anilines
had little effect on the enantioselectivities but a great effect on
the yields of the reactions (Table 2, entries 1–3). Both of the
N-methyl arylamines with electron-withdrawing group (Table 2,
entry 4) or with an electron-donating group (Table 2, entry 5) were
suitable nucleophiles, although a relatively long reaction time was
needed for the latter. When N-methyl naphthylamine 2f was
employed as the nucleophile in the reaction, a high enantioselec-
tivity with a good yield could be obtained (Table 2, entry 6). Under
the promotion of this iridium catalyst, the dialkyl amines 2g and
2h also reacted with 1a, but the asymmetric ring opening products
were obtained in low yields and decreased enantioselectivities
(Table 2, entries 7 and 8). Two additional amines tert-butylamine
and cyclohexanamine only give the desired product in trace
amounts but generated naphthalen-1-ol as a by-product. Besides
secondary amines, primary aryl amines were also found to be
12
13
25
29
51
58
94
96
2l
NH2
Br
NH2 2m
a
The reaction was carried out with oxabenzonorbornadiene 1a (0.3 mmol) and
3.0 equiv of amine 2 (0.9 mmol) in dioxane (2.0 mL) at 70 °C (oil bath temperature)
in the presence of [Ir(COD)Cl]2 (2.5 mol %) and (R)-xylyl-phanephos (6.5 mol %).
b
1-Naphthol was generated as a by-product in most cases.
Isolated yield after neutral alumina column chromatography.
Determined by HPLC with a Chiralcel OD-H or AD-H column.
c
d
applicable nucleophiles in this iridium-catalyzed asymmetric ring
opening reaction. The aryl amines with or without substituents
on the phenyl ring could all react with 1a smoothly and generate
the ring opening products with high enantioselectivities (Table 2,
entries 9–13). It should be noted that the electron-withdrawing
groups on the phenyl ring of aryl amines resulted in higher
enantioselectivities than the electron-donating ones for the
corresponding reactions.
Using N-methylaniline 2a as the nucleophile, oxabenzonorbor-
nadienes with different substituents were also applied as
substrates in this iridium-catalyzed asymmetric ring opening
reaction (Table 3). Compared with those of the amine counterparts,
the electronic properties of the substituents on the phenyl ring of
the oxabenzonorbornadienes had an opposite effect on the
enantioselectivities of the reactions. The electron-donating
groups resulted in higher enantioselectivities than the electron-
withdrawing ones (Table 3, entries 3, 6–4). On the other hand,
the positions of the electron-donating groups on the phenyl ring
of the oxabenzonorbornadienes could also affect the yields of
the reactions greatly. It was found that under the catalysis of this

1356
Y. Zhou et al. / Tetrahedron: Asymmetry 26 (2015) 1354–1359
Table 3
Asymmetric ring opening reactions of different oxabenzonorbornadienes with N-methylaniline 2aa
R2
R2
R2
OH
Me
N
2.5 mol% [Ir(COD)Cl]2
6.5 mol% (R)-xylyl-phanephos
R1
R1
R1
R1
H
N
Ph
O
dioxane, 70 oC
Ph
Me
R2
1a-f
2a
3aa-3fa
Entry
1
Oxabenzonorbornadienes 1
Time (h)
22
Yieldb (%)
75
eec (%)
96
O
1a
Me
O
O
1b
1c
2
3
4
10
8
56 (20)d
48 (21)d
40 (14)d
97
98
86
Me
O
O
Br
1d
1e
O
12
Br
Me
O
O
5
6
90
72
79
81
98
97
Me
OMe
1f
OMe
a
The reaction was carried out with oxabenzonorbornadiene 1 (0.3 mmol) and 3.0 equiv of 2a (0.9 mmol) in dioxane (2.0 mL) at 70 °C (oil bath temperature) in the presence
of [Ir(COD)Cl]2 (2.5 mol %) and (R)-xylyl-phanephos (6.5 mol %).
b
Isolated yield after neutral alumina column chromatography.
Determined by HPLC with a Chiralcel OD-H or AD-H column.
Isolated yield of the corresponding substituted 1-naphthol as the by-product.
c
d
iridium catalyst, the ortho-disubstituted oxabenzonorbornadienes
were easier to convert into the isomerized by-product, substituted
1-naphthols. This competitive consumption of oxabenzonorborna-
dienes could greatly decrease the yields of the asymmetric ring
opening reactions (Table 3, entries 2–4). Better yields were
obtained for the asymmetric ring opening reactions of para-disub-
stituted oxabenzonorbornadienes, although longer reaction times
were needed (Table 3, entries 5 and 6).
were synthesized according to the published procedures.1
Amines were purchased from reagent companies and distilled
before use, while other commercial reagents were used as received
without further purification. Anhydrous dioxane was distilled
from sodium benzophenone ketyl prior to use. 1H NMR and 13C
NMR spectra were recorded on a Bruker-Avance 400 spectrometer.
Chemical shifts (d) are reported in ppm with tetramethylsilane as
internal standard, and J values are given in Hz. The ee values were
determined by Agilent 1260 Series HPLC using Daicel AD-H or
OD-H, chiral columns with a mixture of i-propyl alcohol and
n-hexane as eluent. The absolute configurations were assigned by
comparison of the chiral HPLC data reported in the literature.6a
Melting points were measured on an X-4 melting point
apparatus and are uncorrected. High resolution mass spectra
(HRMS) were performed on a VG Autospec-3000 spectrometer.
Column chromatography was performed with neutral alumina
with petroleum ether and ethyl acetate as eluents.
3. Conclusions
In conclusion, we have found that the complex of [Ir(COD)Cl]2
and (R)-xylyl-phanephos was an efficient catalyst for the asym-
metric ring opening reactions of oxabenzonorbornadienes with
amines. Under the promotion of this iridium catalyst, both primary
amines and secondary amines could react with oxabenzonorborna-
diene 1a smoothly to generally generate the ring opening products
with high enantioselectivities and moderate to good yields. Fur-
thermore, the substituent effects of oxabenzonorbornadienes on
this iridium-catalyzed ring opening reaction have also been inves-
tigated. A mechanism study on the catalytic procedure and further
improvement of this iridium catalyst are currently in progress.
4.2. Typical procedure for the Ir-catalyzed asymmetric ring
opening reactions
At first, [Ir(COD)Cl]2 (5.1 mg, 0.0075 mmol), (R)-xylyl-phane-
phos (13.5 mg, 0.0195 mmol) and 1.0 mL of dioxane were added
to a Schlenk tube in an argon atmosphere. The resulting solution
was stirred at room temperature for 30 min, then a solution of
oxobenzonorbornadiene 1a (43.2 mg, 0.3 mmol) in dioxane
(1.0 mL) was added, and the mixture was stirred for an additional
4. Experimental
4.1. General
20 min. After the addition of N-methylaniline 2a (97.0
0.9 mmol), the mixture was stirred at 70 °C under an argon
ll,
The reactions were carried out under argon atmosphere by using
a Drybox (Mikrouna, Supper 1220/750). Oxabenzonorbornadienes

Y. Zhou et al. / Tetrahedron: Asymmetry 26 (2015) 1354–1359
1357
atmosphere with TLC monitoring until the complete consumption
of 1a. After removing the solvent under reduced pressure, the resi-
due of the reaction solution was then purified by chromatography
on a neutral alumina column to afford the desired product 3aa
(56.1 mg, 75% yield). The enantiomeric excess of the product was
determined to be 96% by HPLC with a Daicel Chiralcel OD-H
column.
7.11–7.09 (m, 1H), 6.98–6.96 (m, 2H), 6.87–6.83 (m, 2H), 6.58–
6.55 (dd, J = 9.8 Hz, 2.5 Hz, 1H), 5.97–5.94 (dd, J = 9.8 Hz, 2.8 Hz,
1H), 5.12–5.09 (d, J = 10.5 Hz, 1H), 4.56–4.52 (dt, J = 10.4 Hz,
2.6 Hz, 1H), 3.78 (s, 3H), 2.81 (s, 3H), 2.64 (s, 1H). The ee of 3ae
was determined by HPLC analysis using Daicel Chiralcel OD-H col-
umn (25 cm  0.46 cm ID), conditions: n-hexane/i-PrOH = 90/10,
0.8 mL/min, 254 nm; tminor = 17.2 min, tmajor = 20.4 min.
4.3. (1R,2R)-2-(Methyl(phenyl)amino)-1,2-dihydronaphthalen-1-
4.8. (1R,2R)-2-(Methyl(naphthalen-2-yl)amino)-1,2-dihydrona-
ol 3aa
phthalen-1-ol 3af
White solid, 75% yield, 96% ee. [
a
]
22 = +31.5 (c 0.34, CH2Cl2). 1
H
Yellow liquid, 56% yield, 97% ee. [a]
22 = +48.5 (c 0.109, CH2Cl2).
D
D
NMR (400 MHz, CDCl3) d 7.56–7.54 (m, 1H), 7.29–7.26 (m, 3H),
7.25–7.24 (m, 1H), 7.13–7.10 (m, 1H), 6.98–6.96 (d, J = 8.6 Hz,
2H), 6.82–6.78 (t, J = 7.3 Hz, 1H), 6.61–5.58 (dd, J = 9.8, 2.4 Hz,
1H), 5.95–5.92 (dd, J = 9.8 Hz, 3.0 Hz, 1H), 5.13–5.10 (dd,
J = 9.8 Hz, 3.2 Hz, 1H), 4.76–4.72 (dt, J = 9.9 Hz, 2.7 Hz, 1H), 2.85
(s, 3H), 2.31–2.30 (d, J = 3.4 Hz, 1H). The ee of 3aa was determined
by HPLC analysis using Daicel Chiralcel OD-H column
(25 cm  0.46 cm ID), conditions: n-hexane/i-PrOH = 90/10,
1.0 mL/min, 254 nm; tmajor = 11.0 min, tminor = 13.2 min.
1H NMR (400 MHz, CDCl3) d 7.59–7.54 (m, 3H), 7.45–7.43 (m, 1H),
7.30–7.10 (m, 6H), 7.02–6.99 (m, 2H), 6.49–6.46 (dd, J = 9.8 Hz,
2.4 Hz, 1H), 5.85–5.81 (dd, J = 9.8 Hz, 2.9 Hz, 1H), 5.04–5.01 (d,
J = 10.0 Hz, 1H), 4.76–4.73 (dt, J = 10.0 Hz, 2.6 Hz, 1H), 2.80 (s,
3H). The ee of 3af was determined by HPLC analysis using Daicel
Chiralcel OD-H column (25 cm  0.46 cm ID), conditions: n-hex-
ane/i-PrOH = 90/10,
tmajor = 28.6 min.
1.0 mL/min,
254 nm;
tminor = 18.5 min,
4.9. (1R,2R)-2-(Dibenzylamino)-1,2-dihydronaphthalen-1-ol 3ag
4.4. (1R,2R)-2-(Ethyl(phenyl)amino)-1,2-dihydronaphthalen-1-
ol 3ab
Colorness oil, 36% yield, 88% ee. [
a
]
22 = À68.8 (c 0.247, CH2Cl2).
D
1H NMR (400 MHz, CDCl3) d 7.52–7.50 (d, J = 6.9 Hz 1H), 7.33–7.32
(d, J = 4.3 Hz, 8H), 7.26–7.17 (m, 4H), 7.05–7.04 (d, J = 6.6 Hz, 1H),
6.57–6.54 (dd, J = 9.9 Hz, 2.3 Hz, 1H), 6.16–6.13 (dd, J = 9.9 Hz,
2.0 Hz, 1H), 5.04–5.01 (d, J = 11.7 Hz, 1H), 3.99–3.96 (d,
J = 13.6 Hz, 2H), 3.69–3.66 (d, J = 11.7 Hz, 1H), 3.62–3.58 (d,
J = 13.6 Hz, 2H), 3.07 (s, 1H). The ee of 3ag was determined by
Colorness oil, 56% yield, 97% ee. [
a
]
22 = À16.7 (c 0.502, CH2Cl2).
D
1H NMR (400 MHz, CDCl3) d 7.53–7.51 (m, 1H), 7.28–7.23 (m, 4H),
7.13–7.11 (m, 1H), 6.96–6.94 (d, J = 8.3 Hz, 2H), 6.79–6.75 (t,
J = 7.2 Hz, 1H), 6.61–6.58 (dd, J = 9.8, 1.9 Hz, 1H), 5.97–5.94 (dd,
J = 9.8, 3.0 Hz, 1H), 5.11–5.09 (d, J = 9.3 Hz, 1H), 4.68–4.66 (d,
J = 9.3 Hz, 1H), 3.37–3.32 (q, J = 7.0 Hz, 2H), 2.37 (s, 1H), 1.16–
1.13 (t, J = 7.0 Hz, 3H). The ee of 3ab was determined by HPLC anal-
ysis using Daicel Chiralcel OD-H column (25 cm  0.46 cm ID),
conditions: n-hexane/i-PrOH = 90/10, 1.0 mL/min, 254 nm;
tmajor = 8.3 min, tminor = 9.8 min.
HPLC
analysis
using
Daicel
Chiralcel
OD-H
column
(25 cm  0.46 cm ID), conditions: n-hexane/i-PrOH = 90/10,
1.0 mL/min, 254 nm; tmajor = 7.5 min, tminor = 8.9 min.
4.10. (1R,2R)-2-(4-Phenylpiperazin-1-yl)-1,2-dihydronaphthalen-
1-ol 3ah
4.5. (1R,2R)-2-(Isopropyl(phenyl)amino)-1,2-dihydronaphthalen-1-
ol 3ac
White solid, 30% yield, 84% ee. [
a
]
22 = À107.6 (c 0.341, CH2Cl2).
D
1H NMR (400 MHz, CDCl3) d 7.59–7.57 (d, J = 7.2 Hz, 1H), 7.28–7.21
(m, 4H), 7.09–7.07 (d, J = 7.2 Hz, 1H), 6.94–6.85 (m, 3H), 6.56–6.53
(dd, J = 9.6 Hz, 1.6 Hz, 1H), 6.16–6.13 (dd, J = 9.6 Hz, 2.0 Hz, 1H),
4.93–4.90 (d, J = 11.2 Hz, 1H), 3.52–3.49 (d, J = 11.6 Hz, 1H), 3.35–
3.16 (m, 5H), 2.97–2.93 (m, 2H), 2.71–2.68 (m, 2H). The ee of 3ag
was determined by HPLC analysis using Daicel Chiralcel AD-H col-
umn (25 cm  0.46 cm ID), conditions: n-hexane/i-PrOH = 95/5,
1.0 mL/min, 254 nm; tminor = 16.0 min, tmajor = 17.4 min.
Yellow oil, 30% yield, 96% ee. [
a]
22 = À66.3 (c 0.228, CH2Cl2). 1H
D
NMR (400 MHz, CDCl3)d 7.32–7.22 (m, 6H), 7.15–7.13 (m, 1H),
6.64–6.57 (m, 3H), 6.08–6.04 (dd, J = 9.48 Hz, 4.32 Hz, 1H),
5.01–4.98 (m, 1H), 4.72–4.70 (m, 1H), 4.24 (s, 1H), 3.88 (s, 1H),
1.46 (s, 6H). The ee of 3ac was determined by HPLC analysis using
Daicel Chiralcel OD-H column (25 cm  0.46 cm ID), conditions:
n-hexane/i-PrOH = 90/10, 1.0 mL/min, 254 nm; tmajor = 4.9 min,
tminor = 5.6 min.
4.11. (1R,2R)-2-(Phenylamino)-1,2-dihydronaphthalen-1-ol 3ai
4.6. (1R,2R)-2-((4-Bromophenyl)(methyl)amino)-1,2-dihydronaph-
thalen-1-ol 3ad
Silvery white solid, 52% yield, 92% ee. [
a
]
22 = À68.8 (c 0.032,
D
CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.46–7.44 (m, 1H), 7.29–
7.24 (m, 2H), 7.20–7.15 (m, 2H), 7.13–7.10 (m, 1H), 6.76–6.68
(m, 1H), 6.55–6.52 (dd, J = 9.6 Hz, 1.5 Hz, 1H), 6.01–5.98 (dd,
J = 9.7 Hz, 3.6 Hz, 1H), 4.83–4.81 (d, J = 7.8 Hz, 1H), 4.32–4.28 (m,
1H). The ee of 3ah was determined by HPLC analysis using Daicel
Chiralcel AD-H column (25 cm  0.46 cm ID), conditions: n-hex-
Colorness oil, 50% yield, 95% ee. [a]
22 = +75.4 (c 0.130, CH2Cl2).
D
1H NMR (400 MHz, CDCl3) d 7.55–7.52 (m, 1H), 7.35–7.28 (m,
4H), 7.14–7.12 (m, 1H), 6.85–6.81 (m, 2H), 6.63–6.60 (dd,
J = 9.7 Hz, 2.4 Hz, 1H), 5.91–5.88 (dd, J = 9.8 Hz, 3.1 Hz, 1H), 5.09–
5.06 (dd, J = 9.4 Hz, 2.1 Hz, 1H), 4.70–4.66 (dt, J = 9.5 Hz, 2.7 Hz,
1H), 2.81 (s, 3H), 2.23–2.22 (m, 1H). The ee of 3ad was determined
by HPLC analysis using Daicel Chiralcel AD-H column
(25 cm  0.46 cm ID), conditions: n-hexane/i-PrOH = 80/20,
1.0 mL/min, 254 nm; tmajor = 8.6 min, tminor = 9.9 min.
ane/i-PrOH = 80/20,
tmajor = 11.8 min.
1.0 mL/min,
254 nm;
tminor = 9.3 min,
4.12. (1R,2R)-2-(p-Tolylamino)-1,2-dihydronaphthalen-1-ol 3aj
4.7. (1R,2R)-2-((4-Methoxyphenyl)(methyl)amino)-1,2-dihydro-
naphthalen-1-ol 3ae
Light yellow solid, 62% yield, 90% ee. [
a
]
22 = À100.4 (c 0.243,
D
CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.51–7.49 (m, 1H), 7.29–
7.27 (t, J = 4.0 Hz, 2H), 7.14–7.12 (m, 1H), 7.04–7.02 (d, J = 8.1 Hz,
2H), 6.74–6.72 (d, J = 8.3 Hz, 2H), 6.56–6.53 (dd, J = 9.7 Hz, 1.4 Hz,
1H), 6.02–6.00 (dd, J = 9.6, 3.3 Hz, 1H), 4.90–4.88 (d, J = 8.4 Hz,
Brown oil, 49% yield, 97% ee. [
NMR (400 MHz, CDCl3) d 7.59–7.57 (m, 1H), 7.31–7.24 (m, 2H),
a]
22 = +21.5 (c 0.0744, CH2Cl2). 1H
D

1358
Y. Zhou et al. / Tetrahedron: Asymmetry 26 (2015) 1354–1359
1H), 4.32–4.29 (m, 1H), 2.85 (s, 1H), 2.26 (s, 3H). The ee of 3ai was
determined by HPLC analysis using Daicel Chiralcel AD-H column
(25 cm  0.46 cm ID), conditions: n-hexane/i-PrOH = 80/20,
1.0 mL/min, 254 nm; tminor = 9.9 min, tmajor = 12.5 min.
column (25 cm  0.46 cm ID), conditions: n-hexane/i-PrOH = 95/5,
0.8 mL/min, 254 nm; tmajor = 50.9 min, tminor = 54.9 min.
4.18. (1R,2R)-6,7-Dibromo-2-(methyl(phenyl)amino)-1,2-dihy-
dronaphthalen-1-ol 3da
4.13.
(1R,2R)-2-((4-Methoxyphenyl)amino)-1,2-dihydronaph-
Yellow solid, 40% yield, 86% ee. [a]
22 = +50.7 (c 0.412, CH2Cl2).
D
thalen-1-ol 3ak
1H NMR (400 MHz, CDCl3) d 7.82 (s, 1H), 7.29–7.25 (m, 2H),
6.96–6.94 (d, J = 8.1 Hz, 2H), 6.85–6.81 (t, J = 7.3 Hz, 1H), 6.47–
6.44 (dd, J = 9.9 Hz, 2.7 Hz, 1H), 6.02–5.99 (dd, J = 9.8 Hz, 2.6 Hz,
1H), 5.08–5.05 (d, J = 11.1 Hz, 1H), 4.72–4.68 (dt, J = 11.1 Hz,
2.6 Hz, 1H), 2.89 (s, 3H), 2.56 (s, 1H). The ee of 3da was determined
by HPLC analysis using Daicel Chiralcel OD-H column
(25 cm  0.46 cm ID), conditions: n-hexane/i-PrOH = 90/10,
0.8 mL/min, 254 nm; tmajor = 18.5 min, tminor = 21.4 min.
White solid, 47% yield, 89% ee. [
a
]
D
22 = À80.3 (c 0.0648, CH2Cl2).
1H NMR (400 MHz, CDCl3) d 7.53–7.51 (m, 1H), 7.30–7.28 (m, 2H),
7.27 (s, 2H), 7.14–7.12 (m, 1H), 6.83–6.76 (m, 4H), 6.55–6.53 (dd,
J = 9.6 Hz, 1.8 Hz, 1H), 6.03–6.00 (dd, J = 9.7 Hz, 3.3 Hz, 1H), 4.89–
4.87 (d, J = 8.7 Hz, 1H), 3.77 (s, 3H). The ee of 3aj was determined
by HPLC analysis using Daicel Chiralcel AD-H column
(25 cm  0.46 cm ID), conditions: n-hexane/i-PrOH = 80/20,
1.0 mL/min, 254 nm; tminor = 14.2 min, tmajor = 18.7 min.
4.19. (1R,2R)-5,8-Dimethyl-2-(methyl(phenyl)amino)-1,2-dihy-
dronaphthalen-1-ol 3ea
4.14.
thalen-1-ol 3al
(1R,2R)-2-((3-Bromophenyl)amino)-1,2-dihydronaph-
Colorness oil, 79% yield, 98% ee. [
a
]
22 = À334 (c 0.628, CH2Cl2).
D
Yellow oil, 51% yield, 94% ee. [a]
22 = À75.5 (c 0.11, CH2Cl2). 1H
1H NMR (400 MHz, CDCl3) d 7.22–7.18 (m, 2H), 6.98–6.91 (m,
3H), 6.88–6.86 (d, J = 8.1 Hz, 2H), 6.72–6.68 (m, 1H), 5.91–5.87
(qd, J = 5.7 Hz, 1.3 Hz, 1H), 4.80 (s, 1H), 4.57–4.56 (d, J = 5.7 Hz,
1H), 2.31–2.30 (m, 6H), 2.24 (s, 3H), 1.60 (s, 1H). The ee of 3ea
was determined by HPLC analysis using Daicel Chiralcel OD-H
column (25 cm  0.46 cm ID), conditions: n-hexane/i-PrOH = 97/3,
0.5 mL/min, 254 nm; tminor = 39.1 min, tmajor = 41.4 min.
D
NMR (400 MHz, CDCl3) d 7.48–7.46 (m, 1H), 7.35–7.28 (m, 2H),
7.18–7.16 (m, 1H), 7.07–7.03 (t, J = 8.3 Hz, 1H), 6.89–6.87 (m,
2H), 6.65–6.59 (m, 2H), 6.02–5.99 (dd, J = 9.6 Hz, 3.8 Hz, 1H),
4.85–4.83 (d, J = 7.3 Hz, 1H), 4.31–4.28 (m, 1H), 2.47 (s, 1H).
The ee of 3ak was determined by HPLC analysis using Daicel
Chiralcel AD-H column (25 cm  0.46 cm ID), conditions:
n-hexane/i-PrOH = 80/20, 1.0 mL/min, 254 nm; tminor = 8.3 min,
tmajor = 11.1 min.
4.20. (1R,2R)-5,8-Dimethoxy-2-(methyl(phenyl)amino)-1,2-dihy-
dronaphthalen-1-ol 3fa
4.15.
(1R,2R)-2-((4-Bromophenyl)amino)-1,2-dihydronaph-
thalen-1-ol 3am
Brownish-yellow solid, 81% yield, 97% ee. [
a
]
22 = À156.5 (c 0.20
D
CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.30–7.24 (m, 2H), 7.19–7.16
(dd, J = 10.0 Hz, 1.7 Hz, 1H), 6.98–6.96 (d, J = 8.0 Hz, 2H), 6.82–6.74
(m, 3H), 5.97–5.93 (td, J = 5.2 Hz, 0.8 Hz, 1H), 5.16–5.15 (d,
J = 1.3 Hz, 1H), 4.70–4.68 (m, 1H), 3.82(s, 3H), 3.78 (s, 3H), 2.54
(s, 3H). The ee of 3fa was determined by HPLC analysis using Daicel
Chiralcel AD-H column (25 cm  0.46 cm ID), conditions: n-hex-
Light yellow solid, 58% yield, 96% ee. [
a]
22 = À70.5 (c 0.095,
D
CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.49–7.46 (m, 1H), 7.33–
7.26 (m, 4H), 7.16–7.14 (m, 1H), 6.66–6.62 (m, 2H), 6.60–6.57
(dd, J = 9.6 Hz, 1.4 Hz, 1H), 6.01–5.98 (dd, J = 9.6 Hz, 3.7 Hz, 1H),
4.86–4.84 (d, J = 7.5 Hz, 1H), 4.30–4.27 (qd, J = 3.7 Hz, 1.7 Hz, 1H),
2.41 (s, 2H). The ee of 3al was determined by HPLC analysis using
Daicel Chiralcel AD-H column (25 cm  0.46 cm ID), conditions:
n-hexane/i-PrOH = 80/20, 1.0 mL/min, 254 nm; tminor = 11.8 min,
tmajor = 13.0 min.
ane/i-PrOH = 95/5,
tmajor = 49.8 min.
1.0 mL/min,
254 nm;
tminor = 44.3 min,
Acknowledgments
4.16. (1R,2R)-6,7-Dimethyl-2-(methyl(phenyl)amino)-1,2-dihy-
dronaphthalen-1-ol 3ba
We thank the National Natural Science Foundation of China
(21362043, 21162040, 21302162) and the Government of Yunnan
Province, China (2012FB170) for financial support.
Yellowish-white solid, 56% yield, 97% ee. [a]
22 = +18.3 (c 0.278,
D
CH2Cl2). 1H NMR (400 MHz, CDCl3) d 7.30–7.24 (m, 3H), 6.97–6.95
(d, J = 8.1 Hz, 2H), 6.91 (s, 1H), 6.81–6.78 (t, J = 7.3 Hz, 1H), 6.57–
6.54(dd, J = 9.8 Hz, 2.3 Hz, 1H), 5.87–5.84(dd, J = 9.7 Hz, 3.2 Hz,
1H), 5.03–5.01(d, J = 9.1 Hz, 1H), 4.71–4.68 (dt, J = 9.1 Hz, 2.8 Hz,
1H), 2.81 (s, 3H), 2.28–2.26 (d, J = 8.7 Hz, 7H). The ee of 3ba was
determined by HPLC analysis using Daicel Chiralcel OD-H column
(25 cm  0.46 cm ID), conditions: n-hexane/i-PrOH = 90/10,
0.8 mL/min, 254 nm; tmajor = 12.0 min, tminor = 15.6 min.
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